Trial Outcomes & Findings for Statin Use in Patients With Acute VTE (NCT NCT02331095)

NCT ID: NCT02331095

Last Updated: 2020-10-19

Results Overview

Determine the reduction of endogenous thrombin potential measured by Thrombin Generation Assay (TGA) at 3 months in the "anticoagulation +atorvastatin" arm as compared to the "anticoagulation" arm.

• Recruitment status: TERMINATED
• Study phase: EARLY_PHASE1
• Target enrollment: 21 participants
• Primary outcome timeframe: 3 Months
• Results posted on: 2020-10-19

Participant Flow

Participant milestones

Measure	Anticoagulation Patients will be treated with warfarin with dose adjusted to goal International Normalized Ratio (INR) of 2-3 or rivaroxaban standard dose (15 mg twice daily for 3 weeks then 20 mg daily)	Atorvastatin + Anticoagulation In addition to warfarin or rivaroxaban as standard anticoagulation, patients will be given concurrent atorvastatin 40 mg daily for 3 months, starting from the time of enrollment Atorvastatin: Atorvastatin belongs to the "statin" class of drugs, and is routinely used for prevention of cardiovascular diseases and/or reduction of cholesterol levels. It has been shown to decrease the risk of first venous thromboembolism in an otherwise healthy population with elevated high-sensitivity C-reactive protein (hs-CRP). Warfarin: Warfarin is a standard anticoagulation in the treatment for venous thromboembolism. The dose will be adjusted to goal INR of 2-3. Atorvastatin: Atorvastatin belongs to the "statin" class of drugs, and is routinely used for prevention of cardiovascular diseases and/or reduction of cholesterol levels. It has been shown to decrease the risk of first venous thromboembolism in an otherwise healthy population with elevated high-sensitivity C-reactive protein (hs-CRP).
Overall Study STARTED	11	10
Overall Study COMPLETED	7	9
Overall Study NOT COMPLETED	4	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Statin Use in Patients With Acute VTE

Baseline characteristics by cohort

Measure	Anticoagulation n=11 Participants Patients will be treated with warfarin with dose adjusted to goal International Normalized Ratio (INR) of 2-3 or rivaroxaban standard dose (15 mg twice daily for 3 weeks then 20 mg daily)	Atorvastatin + Anticoagulation n=10 Participants In addition to warfarin or rivaroxaban as standard anticoagulation, patients will be given concurrent atorvastatin 40 mg daily for 3 months, starting from the time of enrollment Atorvastatin: Atorvastatin belongs to the "statin" class of drugs, and is routinely used for prevention of cardiovascular diseases and/or reduction of cholesterol levels. It has been shown to decrease the risk of first venous thromboembolism in an otherwise healthy population with elevated high-sensitivity C-reactive protein (hs-CRP). Warfarin: Warfarin is a standard anticoagulation in the treatment for venous thromboembolism. The dose will be adjusted to goal INR of 2-3. Atorvastatin: Atorvastatin belongs to the "statin" class of drugs, and is routinely used for prevention of cardiovascular diseases and/or reduction of cholesterol levels. It has been shown to decrease the risk of first venous thromboembolism in an otherwise healthy population with elevated high-sensitivity C-reactive protein (hs-CRP).	Total n=21 Participants Total of all reporting groups
Age, Continuous	54 years n=5 Participants	57.5 years n=7 Participants	55 years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized Caucasions	10 Participants n=5 Participants	7 Participants n=7 Participants	17 Participants n=5 Participants
Race/Ethnicity, Customized African Americans	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Pulmonary Embolism (PE) (in addition to DVT)	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Provoked	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Hemoglobin (g/dL)	13.7 g/dL n=5 Participants	12.1 g/dL n=7 Participants	13.4 g/dL n=5 Participants
Platelet count (K/uL)	276 K/uL n=5 Participants	301 K/uL n=7 Participants	290 K/uL n=5 Participants
Creatinine (mg/dL)	0.82 mg/dL n=5 Participants	0.74 mg/dL n=7 Participants	0.77 mg/dL n=5 Participants

PRIMARY outcome

Timeframe: 3 Months

Determine the reduction of endogenous thrombin potential measured by Thrombin Generation Assay (TGA) at 3 months in the "anticoagulation +atorvastatin" arm as compared to the "anticoagulation" arm.

Outcome measures

Measure	Anticoagulation n=11 Participants Patients will be treated with warfarin with dose adjusted to goal International Normalized Ratio (INR) of 2-3 or rivaroxaban standard dose (15 mg twice daily for 3 weeks then 20 mg daily)	Atorvastatin + Anticoagulation n=10 Participants In addition to warfarin or rivaroxaban as standard anticoagulation, patients will be given concurrent atorvastatin 40 mg daily for 3 months, starting from the time of enrollment Atorvastatin: Atorvastatin belongs to the "statin" class of drugs, and is routinely used for prevention of cardiovascular diseases and/or reduction of cholesterol levels. It has been shown to decrease the risk of first venous thromboembolism in an otherwise healthy population with elevated high-sensitivity C-reactive protein (hs-CRP). Warfarin: Warfarin is a standard anticoagulation in the treatment for venous thromboembolism. The dose will be adjusted to goal INR of 2-3.
The Reduction of Endogenous Thrombin Potential Enrollment	1155 nM*min Interval 0.0 to 1853.0	1440 nM*min Interval 0.0 to 3190.0
The Reduction of Endogenous Thrombin Potential 3 Months	1275 nM*min Interval 0.0 to 2562.0	1143 nM*min Interval 60.0 to 3766.0

PRIMARY outcome

Timeframe: 3 Months

Determine the reduction of thrombin peak concentration measured by Thrombin Generation Assay (TGA) at 3 months in the "anticoagulation +atorvastatin" arm as compared to the "anticoagulation" arm.

Outcome measures

Measure	Anticoagulation n=11 Participants Patients will be treated with warfarin with dose adjusted to goal International Normalized Ratio (INR) of 2-3 or rivaroxaban standard dose (15 mg twice daily for 3 weeks then 20 mg daily)	Atorvastatin + Anticoagulation n=10 Participants In addition to warfarin or rivaroxaban as standard anticoagulation, patients will be given concurrent atorvastatin 40 mg daily for 3 months, starting from the time of enrollment Atorvastatin: Atorvastatin belongs to the "statin" class of drugs, and is routinely used for prevention of cardiovascular diseases and/or reduction of cholesterol levels. It has been shown to decrease the risk of first venous thromboembolism in an otherwise healthy population with elevated high-sensitivity C-reactive protein (hs-CRP). Warfarin: Warfarin is a standard anticoagulation in the treatment for venous thromboembolism. The dose will be adjusted to goal INR of 2-3.
The Reduction of Peak Thrombin Concentration Enrollment	37 nM Interval 0.0 to 157.0	67 nM Interval 0.0 to 123.0
The Reduction of Peak Thrombin Concentration 3 Months	54 nM Interval 0.0 to 149.0	48 nM Interval 11.0 to 253.0

SECONDARY outcome

Timeframe: 3 months and 9 months

Recurrent PE was defined as new filling defect(s) seen on CT angiogram or a new high-probability ventilation-perfusion lung scan (22, 23). Recurrent DVT was defined as new uncompressible segments seen on vascular Doppler ultrasonography in a previously uninvolved limb, clearly extending from the prior thrombosis, or a new venous segment in a previously involved limb.

Outcome measures

Measure	Anticoagulation n=11 Participants Patients will be treated with warfarin with dose adjusted to goal International Normalized Ratio (INR) of 2-3 or rivaroxaban standard dose (15 mg twice daily for 3 weeks then 20 mg daily)	Atorvastatin + Anticoagulation n=10 Participants In addition to warfarin or rivaroxaban as standard anticoagulation, patients will be given concurrent atorvastatin 40 mg daily for 3 months, starting from the time of enrollment Atorvastatin: Atorvastatin belongs to the "statin" class of drugs, and is routinely used for prevention of cardiovascular diseases and/or reduction of cholesterol levels. It has been shown to decrease the risk of first venous thromboembolism in an otherwise healthy population with elevated high-sensitivity C-reactive protein (hs-CRP). Warfarin: Warfarin is a standard anticoagulation in the treatment for venous thromboembolism. The dose will be adjusted to goal INR of 2-3.
The Composite Rate of Recurrent Venous Thromboembolism (VTE) and VTE Related Mortality 3 Months	0 Participants	0 Participants
The Composite Rate of Recurrent Venous Thromboembolism (VTE) and VTE Related Mortality 9 Months	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 3 months and 9 months

Arterial thromboembolism was defined a new myocardial infarction (based on typical electrocardiographic findings and/or elevation of cardiac enzymes) or cerebral vascular accident (based on clinical syndrome of development of focal or global loss of brain function thought to be vascular in origin, confirmed by appropriate standard imaging studies).

Outcome measures

Measure	Anticoagulation n=11 Participants Patients will be treated with warfarin with dose adjusted to goal International Normalized Ratio (INR) of 2-3 or rivaroxaban standard dose (15 mg twice daily for 3 weeks then 20 mg daily)	Atorvastatin + Anticoagulation n=10 Participants In addition to warfarin or rivaroxaban as standard anticoagulation, patients will be given concurrent atorvastatin 40 mg daily for 3 months, starting from the time of enrollment Atorvastatin: Atorvastatin belongs to the "statin" class of drugs, and is routinely used for prevention of cardiovascular diseases and/or reduction of cholesterol levels. It has been shown to decrease the risk of first venous thromboembolism in an otherwise healthy population with elevated high-sensitivity C-reactive protein (hs-CRP). Warfarin: Warfarin is a standard anticoagulation in the treatment for venous thromboembolism. The dose will be adjusted to goal INR of 2-3.
The Rate of Arterial Thrombotic Events 3 Months	0 Participants	0 Participants
The Rate of Arterial Thrombotic Events 9 Months	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 3 Months

Residual venous obstruction was assed by Doppler Ultrasonography. Residual chronic DVT (to any degree) was reported.

Outcome measures

Measure	Anticoagulation n=11 Participants Patients will be treated with warfarin with dose adjusted to goal International Normalized Ratio (INR) of 2-3 or rivaroxaban standard dose (15 mg twice daily for 3 weeks then 20 mg daily)	Atorvastatin + Anticoagulation n=10 Participants In addition to warfarin or rivaroxaban as standard anticoagulation, patients will be given concurrent atorvastatin 40 mg daily for 3 months, starting from the time of enrollment Atorvastatin: Atorvastatin belongs to the "statin" class of drugs, and is routinely used for prevention of cardiovascular diseases and/or reduction of cholesterol levels. It has been shown to decrease the risk of first venous thromboembolism in an otherwise healthy population with elevated high-sensitivity C-reactive protein (hs-CRP). Warfarin: Warfarin is a standard anticoagulation in the treatment for venous thromboembolism. The dose will be adjusted to goal INR of 2-3.
The Rate of Residual (Chronic) Vein Obstruction by Doppler Ultrasound	8 Participants	8 Participants

SECONDARY outcome

Timeframe: 3 Months

The Villata score for Post-Thrombotic Syndrome (PTS) stratifies the severity of post-thrombotic syndrome in lower extremity DVT. The score contains a combination of 5 subjective symptoms as reported by the patient (cramps, itching, pins and needles, heaviness, and pain) and 6 objective signs measured by a provider (edema, skin induration, hyperpigmentation, prominent veins on legs, redness, and tenderness on calf compression). Each sign is scaled from 0 (no or minimal) to 3 (severe) with a total score ranged from 0 to 33. Higher scores represent more severe disease.

Outcome measures

Measure	Anticoagulation n=11 Participants Patients will be treated with warfarin with dose adjusted to goal International Normalized Ratio (INR) of 2-3 or rivaroxaban standard dose (15 mg twice daily for 3 weeks then 20 mg daily)	Atorvastatin + Anticoagulation n=10 Participants In addition to warfarin or rivaroxaban as standard anticoagulation, patients will be given concurrent atorvastatin 40 mg daily for 3 months, starting from the time of enrollment Atorvastatin: Atorvastatin belongs to the "statin" class of drugs, and is routinely used for prevention of cardiovascular diseases and/or reduction of cholesterol levels. It has been shown to decrease the risk of first venous thromboembolism in an otherwise healthy population with elevated high-sensitivity C-reactive protein (hs-CRP). Warfarin: Warfarin is a standard anticoagulation in the treatment for venous thromboembolism. The dose will be adjusted to goal INR of 2-3.
The Reduction of Clinical Post-thrombotic Syndrome (PTS), as Objectively Evaluated With Villalta Scoring System Enrollment	7 scores on a scale Interval 0.0 to 18.0	4.5 scores on a scale Interval 2.0 to 21.0
The Reduction of Clinical Post-thrombotic Syndrome (PTS), as Objectively Evaluated With Villalta Scoring System 3 Months	6 scores on a scale Interval 1.0 to 13.0	3.5 scores on a scale Interval 0.0 to 15.0

SECONDARY outcome

Timeframe: 3 months and 9 months

Major bleeding events were defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria, with overt bleeding in critical organs (e.g. central nervous system, retroperitoneum), a >2 gram/dL drop in hemoglobin from baseline, or requiring at least two units of packed red blood cell transfusion meeting the criteria for major bleeding. Clinically relevant, non-major bleeding (CRNMB) events were defined as any other bleeding events reported by patients but not otherwise meeting the above listed criteria for major bleeding.

Outcome measures

Measure	Anticoagulation n=11 Participants Patients will be treated with warfarin with dose adjusted to goal International Normalized Ratio (INR) of 2-3 or rivaroxaban standard dose (15 mg twice daily for 3 weeks then 20 mg daily)	Atorvastatin + Anticoagulation n=10 Participants In addition to warfarin or rivaroxaban as standard anticoagulation, patients will be given concurrent atorvastatin 40 mg daily for 3 months, starting from the time of enrollment Atorvastatin: Atorvastatin belongs to the "statin" class of drugs, and is routinely used for prevention of cardiovascular diseases and/or reduction of cholesterol levels. It has been shown to decrease the risk of first venous thromboembolism in an otherwise healthy population with elevated high-sensitivity C-reactive protein (hs-CRP). Warfarin: Warfarin is a standard anticoagulation in the treatment for venous thromboembolism. The dose will be adjusted to goal INR of 2-3.
The Rate of Major, Non-major, and All Hemorrhages Defined by the International Society on Thrombosis and Haemostasis (ISTH) Criteria 3 Months	0 Participants	0 Participants
The Rate of Major, Non-major, and All Hemorrhages Defined by the International Society on Thrombosis and Haemostasis (ISTH) Criteria 9 Months	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 3 Months

Outcome measures

Measure	Anticoagulation n=11 Participants Patients will be treated with warfarin with dose adjusted to goal International Normalized Ratio (INR) of 2-3 or rivaroxaban standard dose (15 mg twice daily for 3 weeks then 20 mg daily)	Atorvastatin + Anticoagulation n=10 Participants In addition to warfarin or rivaroxaban as standard anticoagulation, patients will be given concurrent atorvastatin 40 mg daily for 3 months, starting from the time of enrollment Atorvastatin: Atorvastatin belongs to the "statin" class of drugs, and is routinely used for prevention of cardiovascular diseases and/or reduction of cholesterol levels. It has been shown to decrease the risk of first venous thromboembolism in an otherwise healthy population with elevated high-sensitivity C-reactive protein (hs-CRP). Warfarin: Warfarin is a standard anticoagulation in the treatment for venous thromboembolism. The dose will be adjusted to goal INR of 2-3.
Change in the Levels of D-Dimer at 3 Months Enrollment	2.12 mcg/mL FEU Interval 0.88 to 13.78	2.2 mcg/mL FEU Interval 0.6 to 5.42
Change in the Levels of D-Dimer at 3 Months 3 Months	0.36 mcg/mL FEU Interval 0.27 to 0.71	0.59 mcg/mL FEU Interval 0.27 to 1.23

SECONDARY outcome

Timeframe: 3 Months

C-Reactive (CRP) was measured using high sensitivity.

Outcome measures

Measure	Anticoagulation n=11 Participants Patients will be treated with warfarin with dose adjusted to goal International Normalized Ratio (INR) of 2-3 or rivaroxaban standard dose (15 mg twice daily for 3 weeks then 20 mg daily)	Atorvastatin + Anticoagulation n=10 Participants In addition to warfarin or rivaroxaban as standard anticoagulation, patients will be given concurrent atorvastatin 40 mg daily for 3 months, starting from the time of enrollment Atorvastatin: Atorvastatin belongs to the "statin" class of drugs, and is routinely used for prevention of cardiovascular diseases and/or reduction of cholesterol levels. It has been shown to decrease the risk of first venous thromboembolism in an otherwise healthy population with elevated high-sensitivity C-reactive protein (hs-CRP). Warfarin: Warfarin is a standard anticoagulation in the treatment for venous thromboembolism. The dose will be adjusted to goal INR of 2-3.
Change in the Levels of C-Reactive Protein at 3 Months Enrollment	5.5 mg/L Interval 2.0 to 51.4	7.0 mg/L Interval 2.0 to 42.4
Change in the Levels of C-Reactive Protein at 3 Months 3 Months	3.9 mg/L Interval 0.6 to 15.7	5.1 mg/L Interval 0.9 to 21.1

SECONDARY outcome

Timeframe: 3 Months

Outcome measures

Measure	Anticoagulation n=11 Participants Patients will be treated with warfarin with dose adjusted to goal International Normalized Ratio (INR) of 2-3 or rivaroxaban standard dose (15 mg twice daily for 3 weeks then 20 mg daily)	Atorvastatin + Anticoagulation n=10 Participants In addition to warfarin or rivaroxaban as standard anticoagulation, patients will be given concurrent atorvastatin 40 mg daily for 3 months, starting from the time of enrollment Atorvastatin: Atorvastatin belongs to the "statin" class of drugs, and is routinely used for prevention of cardiovascular diseases and/or reduction of cholesterol levels. It has been shown to decrease the risk of first venous thromboembolism in an otherwise healthy population with elevated high-sensitivity C-reactive protein (hs-CRP). Warfarin: Warfarin is a standard anticoagulation in the treatment for venous thromboembolism. The dose will be adjusted to goal INR of 2-3.
Change in Low-Density Lipoproteins (LDL) at 3 Months Enrollment	123.8 mg/dL Standard Deviation 22.73	116.9 mg/dL Standard Deviation 43.07
Change in Low-Density Lipoproteins (LDL) at 3 Months 3 Months	115.9 mg/dL Standard Deviation 30.63	76.1 mg/dL Standard Deviation 26.02

SECONDARY outcome

Timeframe: 3 Months

Outcome measures

Measure	Anticoagulation n=11 Participants Patients will be treated with warfarin with dose adjusted to goal International Normalized Ratio (INR) of 2-3 or rivaroxaban standard dose (15 mg twice daily for 3 weeks then 20 mg daily)	Atorvastatin + Anticoagulation n=10 Participants In addition to warfarin or rivaroxaban as standard anticoagulation, patients will be given concurrent atorvastatin 40 mg daily for 3 months, starting from the time of enrollment Atorvastatin: Atorvastatin belongs to the "statin" class of drugs, and is routinely used for prevention of cardiovascular diseases and/or reduction of cholesterol levels. It has been shown to decrease the risk of first venous thromboembolism in an otherwise healthy population with elevated high-sensitivity C-reactive protein (hs-CRP). Warfarin: Warfarin is a standard anticoagulation in the treatment for venous thromboembolism. The dose will be adjusted to goal INR of 2-3.
Change in Triglyceride Levels at 3 Months Enrollment	130.5 mg/dL Standard Deviation 47.69	157.9 mg/dL Standard Deviation 83.06
Change in Triglyceride Levels at 3 Months 3 Months	127.4 mg/dL Standard Deviation 60.45	135.3 mg/dL Standard Deviation 83.79

Adverse Events

Anticoagulation

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Atorvastatin + Anticoagulation

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Tzu-Fei Wang

The Ohio State University

Phone: 614-366-8366

Email: tzufeiwang@gmail.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place